Factors Inducing Renal Shut-Down From Lysed Erythrocytes

Maluf, N. S. Rustum

doi:10.1097/00000658-194907000-00007

Cited by 50 publications

(7 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The present study indicates that a reproducible and significant renal functional lesion can be produced in the dehydrated rat by the intravenous injection of hemoglobin. In accord with the observations of others (8,9) hemoglobin injection in normally hydrated animals, not subjected to measures which produce renal ischemia, failed to produce significant renal failure. In the present study the combination of ether anesthesia and dehydration served to render the kidney susceptible to the deleterious effects of hemoglobinemia.…”

Section: Discussionsupporting

confidence: 81%

The Renal Lesion Associated With Hemoglobinemia

Jaenike

1966

The Journal of Experimental Medicine

View full text Add to dashboard Cite

The precise mechanisms involved in the association of hemoglobinemia with acute renal failure remain unknown. The difficulties in studying this problem in patients are manifold, consequently the bulk of the investigation in this area has necessarily involved experimentally produced lesions in the laboratory animal. Largely as a result of such studies a variety of differing and conflicting hypotheses concerning the pathogenesis of this renal lesion have arisen. Perhaps the most favored of these are the suggestions that (a) tubular blockage by precipitated hemoglobin is the primary cause of excretory failure in the affected kidney, and (b) some undefined factor or factors produce a primary reduction in glomerular filtration rate, presumably as a consequence of renal ischemia. Carefully performed studies may be cited in support of either the first (1, 2) or second (3, 4) of these hypotheses. In addition, other explanations for the renal failure have been considered, particularly the role of abnormal back diffusion of tubular fluid through damaged tubular epithelial structures and the effect of renal edema in reducing renal blood flow and filtration rate. The establishment of an experimental model of a clinical renal disease in the laboratory animal affords the opportunity of making accurate functional measurements of the evolution of the lesion and of correlating structural alterations at each stage of the disorder with the corresponding functional data. This does not appear to have been accomplished with acute renal failure associated with hemoglobinemia. This lack of serial functional and morphological studies of a standard lesion may in part account for the conflicting views regarding the pathogenesis of this disorder. Consequently the present study was designed, with the ultimate objective of defining the mechanisms underlying the renal functional failure associated with this lesion.The present report describes a relatively simple method for the production of acute renal failure in the rat by the intravenous injection of hemoglobin. The lesion is reversible and relatively uniform in its functional and structural manifestations. Certain of the factors which influence its production and degree of severity have been examined. The functional evolution of the lesion, from its

show abstract

Section: Discussionsupporting

confidence: 81%

The Renal Lesion Associated With Hemoglobinemia

Jaenike

1966

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…This relationship between the development of oliguric acute renal failure and dehydration has been reported to exist in other experimental models (39,42), as well as in human disease (43). The adverse effect of dehydration has been attributed to a direct effect of antidiuretic hormone (ADH) on urinary concentration and flow rate in the distal segments of the nephron (39,44,45).…”

Section: Resultsmentioning

confidence: 82%

Glycerol-induced hemoglobinuric acute renal failure in the rat. I. Micropuncture study of the development of oliguria.

Oken¹,

Arce²,

Wilson³

1966

J. Clin. Invest.

217

126

View full text Add to dashboard Cite

The oliguria of acute renal failure has been attributed to tubular obstruction (1-12), "leakage" of the glomerular filtrate through rents in the tubular wall (13)(14)(15)(16)(17)(18)(19), and vascular mechanisms of various types (20)(21)(22)(23)(24)(25). In a previous paper, it was shown that the oliguria of mercury-induced acute renal failure in the rat reflects a primary decrease in glomerular filtration rate and cannot be attributed to tubular mechanisms (26). The applicability of these findings to most types of acute renal failure occurring in humans may be questioned, however, because of the very dissimilar etiologies and the known effect of large doses of mercury on the renal circulation (27). The present study concerns hours before glycerol injection. They lost an average of 8% of body weight in the period of dehydration, during which time their food intake was one-third less than that of nondehydrated animals. Blood samples were obtained by cardiac puncture from a number of glycerolinjected animals and dehydrated control rats that were exempted from micropuncture studies to determine the change in their blood urea nitrogen (BUN) occurring over a 48-hour period. BUN was measured on 0.2-ml samples by a modification of the urease method of Gentzkow (28). Urinary osmolalities were determined with an Advanced osmometer.Acute renal failure was induced by injecting 50%o glycerol in water into the muscle of both hind limbs at a total dose of 10 ml per kg of body weight. Within 2 hours after this injection, the urine was found to be burgundy red in color due to the presence of heme pigments.The animals were subjected to micropuncture experiments at times ranging from 30 minutes to 26 hours after glycerol injection. They were anesthetized with sodium pentobarbital given intraperitoneally at a dose of 40 to 50 mg per kg body weight. Their blood pressure was monitored as described earlier (26) either by a tail cuff microphone method or intra-arterial manometry. Although hypotension typically did not occur, animals whose mean arterial blood pressure was less than 85 mm Hg were excluded from micropuncture study. The left kidney was exposed through an abdominal incision and carefully dissected free of the perirenal fat. The renal hilus was disturbed as little as possible, and the renal capsule was left intact. The kidney was placed in a Lucite holder to minimize its displacement with respiration. Its surface was covered with warm mineral oil to prevent drying and to aid in visualization of the renal structures.Micropuncture methods were those described in an earlier paper (26). In short, proximal tubular hydrostatic pressure was measured by a modification of the manometric method of Wirz (29), using a water manometer to obtain maximal definition of the end point. The manometer was calibrated at zero pressure before each measurement. Glomerular filtration rate and fractional water absorption were determined at least 30 minutes after the injection of 40 ,uc of "C-labeled inulin 1 in 0.3 to 0.5 ml of 140 mM NaCl. Labele...

show abstract

“…Malgré l'émission massive d'urines très diluées au moment où l'on déclenche l'hémo globinurie par injection de glycérol, ces animaux développent une insuffisance rénale aiguë. La sévérité de l'insuffisance rénale est intermédiaire entre celle des Dehydration has been shown to be a potent predisposing factor in the development of acute renal failure (6,11,12). This effect has been attributed in the past to increased urine concentration and slowed flow through distal segments o f the kidney facilitating tubule ob struction with casts.…”

unclassified

The Role of the Concentration Mechanism in the Development of Acute Renal Failure: Micropuncture Studies Using Diabetes Insipidus Rats

Wilson

Thiel

Arce

et al. 1969

Nephron

View full text Add to dashboard Cite

The role of the concentrating mechanism in the potentiation of acute renal failure by dehydration has been studied using rats with complete diabetes insipidus. These rats were shown to be continually dehydrated even when allowed free access to water. Despite massive volumes of highly dilute urine at the time that hemoglobinuria was induced by glycerol injection, these animals developed acute renal insufficiency whose severity was intermediate between that of non-dehydrated and severely dehydrated normal rats treated similarly. Micropuncture experiments showed the appearance of the kidney in vivo and the functional abnormalities of the three types of rats to be qualitatively identical. It appears that dehydration’s effect on hemoglobinuric acute renal failure is independent of the concentrating mechanism and correlates well with plasma volume depletion. It is suggested that factors other than ADH titre, high urine concentration and low flow rate are the prime determinants of the effect of dehydration on hemoglobinuric acute renal failure in the rat.

show abstract

Factors Inducing Renal Shut-Down From Lysed Erythrocytes

Cited by 50 publications

References 5 publications

The Renal Lesion Associated With Hemoglobinemia

The Renal Lesion Associated With Hemoglobinemia

Glycerol-induced hemoglobinuric acute renal failure in the rat. I. Micropuncture study of the development of oliguria.

The Role of the Concentration Mechanism in the Development of Acute Renal Failure: Micropuncture Studies Using Diabetes Insipidus Rats

Contact Info

Product

Resources

About